Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development.
Tissue and molecular heterogeneities are present in the developing secondary palate along the anteroposterior (AP) axis in mice. Here, we show that Wnt5a and its receptor Ror2 are expressed in a graded manner along the AP axis of the palate. Wnt5a deficiency leads to a complete cleft of the secondary palate, which exhibits distinct phenotypic alterations at histological, cellular and molecular levels in the anterior and posterior regions of the palate. We demonstrate that there is directional cell migration within the developing palate. In the absence of Wnt5a, this directional cell migration does not occur. Genetic studies and in vitro organ culture assays further demonstrate a role for Ror2 in mediating Wnt5a signaling in the regulation of cell proliferation and migration during palate development. Our results reveal distinct regulatory roles for Wnt5a in gene expression and cell proliferation along the AP axis of the developing palate, and an essential role for Wnt5a in the regulation of directional cell migration.
He
Fenglei
F
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Xiong
Wei
W
Yu
Xueyan
X
Espinoza-Lewis
Ramon
R
Liu
Chao
C
Gu
Shuping
S
Nishita
Michiru
M
Suzuki
Kentaro
K
Yamada
Gen
G
Minami
Yasuhiro
Y
Chen
Yiping
Y
D000818:Animals; D019521:Body Patterning; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D002972:Cleft Palate / Q000201:enzymology / Q000473:pathology; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008322:Mammals / Q000196:embryology*; D008648:Mesoderm / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010159:Palate / Q000166:cytology* / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D051153:Wnt Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse; D001973:Bromodeoxyuridine